Brain researcher building new experimental platform

Sven Nelander has been researching brain diseases for 20 years. In his latest project, which has SEK 60 million in funding from the Swedish Foundation for Strategic Research (SSF), he and several partners aim to build an experimental platform consisting of small, advanced models of the brain. The aim is to develop individually tailored methods of treating diseases such as cancer tumours and vascular malformations.

“Traditionally, researchers often use animal models, which, while similar to humans, are expensive, time-consuming and sometimes ethically problematic,” Nelander explains.

“Simpler modelling systems, such as cell cultures, offer speed and flexibility but lack relevance to the real disease.”

Nelander and his research team are therefore focusing on an intermediate step: advanced organoids, small three-dimensional models that better mimic the human brain and its diseases.

Building a more complex system

His goal is to build a more complex modelling system, where differences between samples from different patients can be preserved in the experiments.

“We want to develop a flexible platform that both reflects the biology of the disease and enables work at scale. We therefore intend to set up a platform to study diseases of the central nervous system using organoids.”

An organoid consists of stem cells that have been programmed to be a ‘developing brain’. This is an established technique, but Nelander’s research team wants to take it a step further by also inserting blood vessels into the organoids.

“This is important because it is difficult for medicines to enter the brain through the so-called blood-brain barrier.”

The vascularised organoids are placed in microfluidic chips – small systems of channels where nutrient solution circulates, mimicking blood flow. The technology is being developed in collaboration with researchers at the Ångström Laboratory.

Using cell samples from patients

The project also builds on new biobanks in Uppsala – an invaluable resource for linking the models to real patient cases, Nelander says.

“To begin with, we will focus on brain cancer in both children and adults. We also have a collection of samples from patients with congenital vascular malformations of the brain.”

Brain tumours and vascular malformations have something in common – the behaviour of cells varies over time. The researchers will therefore use the new platform to try to reprogramme the cells, which will include filming the cells and using CRISPR technology to insert luminescent markers into them.

The final part of the project involves using computational methods and AI to guide the search for treatments.

Building on interdisciplinarity

The whole project is based on interdisciplinary cooperation. Eight research groups at Uppsala University and Chalmers have joined forces and applied for the grant from SSF. In addition, the project involves two companies specialising in tissue analysis and in transporting biological drugs across the blood-brain barrier.

Nelander himself tried out different tracks during his education.

“At first I studied maths but realised that I was not a mathematician. Then I started studying medicine and realised that I wasn’t a doctor either, so I went into research instead.”

He started on his thesis at a time when the field of genomics was growing rapidly. Somewhere along the way, he settled on the combination of computation and experimentation. After completing his doctoral thesis, he did a postdoc at a cancer institute in the United States.

Fantastic sample collections

Back in Sweden, he and his family moved to Uppsala.

“When I had the opportunity to start a research group here in Uppsala, I discovered the fantastic sample collections, which have been built up since around the late 1960s. We have built a research activity that combines old biobanks, modern laboratory methods and brand new computational methodology.”

The platform to study brain diseases is part of this and could ultimately become a resource for researchers throughout Sweden.

“A long-term goal is to be able to use the platform to test cells in new patients and try at least to come up with recommendations for treatment. This would mean actually linking these functional tests with healthcare. We hope to drive technological innovation, precision medicine and also basic research on these diseases, which are still not fully understood.”

Great need for research

In the field of brain diseases specifically, there is a great need for research, while at the same time the process of drug development involves considerable risk. Studies often fail, partly because the brain is so complex and partly because it is difficult for the drug to cross the blood-brain barrier.

“There are many different cell types interacting in complex ways in an environment that does everything it can to expel foreign chemicals back into the bloodstream,” says Nelander.

“Now we can lower the risk by first obtaining more detailed information about candidate treatments, before proceeding with extremely expensive animal trials that risk failing.”

Building partnerships

Nelander joined Uppsala University in 2012. Around the same time, SciLifeLab, a national life sciences research centre, was launched.

“There are excellent conditions for interdisciplinary research in Uppsala. We have a great opportunity to mount a united campaign against brain diseases.”

He is keen to highlight the unique resources and expertise brought together in his latest project – in mathematics at Chalmers, technology development at the Ångström Laboratory and medical research at the Rudbeck Laboratory.

“For me, interdisciplinarity is about more than technology – it’s about creating a working environment where ideas have space and people dare to collaborate. In a way, that has become what drives me.”

Annica Hulth